Matta H, Surabhi R M, Zhao J, Punj V, Sun Q, Schamus S, Mazzacurati L, Chaudhary P M
Department of Medicine, Division of Hematology-Oncology and the Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA 15213-1863, USA.
Oncogene. 2007 Mar 8;26(11):1656-60. doi: 10.1038/sj.onc.1209931. Epub 2006 Aug 28.
Human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus, is linked to the development of Kaposi's sarcoma, a disease characterized by the presence of distinctive proliferating spindle-like cells. Although HHV8 can induce spindle cell transformation of vascular endothelial cells in vitro, the viral gene(s) responsible for this phenotype remain to be identified. We demonstrate that expression of HHV8-encoded viral Fas-associated death domain protein-like IL-1beta-converting enzyme inhibitory protein K13 is sufficient to induce spindle cell phenotype in human umbilical vein endothelial cells (HUVEC), which is associated with the activation of the nuclear factor-kappaB (NF-kappaB) pathway and can be blocked by Bay-11-7082, a specific inhibitor of this pathway. K13 induces the expression of several genes known to be upregulated in HHV8-transformed vascular endothelial cells, such as interleukin (IL)-6, IL-8, CXC ligand 3 (CXCL3), orphan G protein coupled receptor (RDC1), cyclooxygenase-2 (COX-2) and dual-specificity phosphatase 5 (DUSP5). Furthermore, similar to K13, HHV8-induced spindle cell transformation of HUVEC is associated with NF-kappaB activation and can be blocked by Bay-11-7082. Thus, ectopic expression of a single latent gene of HHV8 is sufficient for the acquisition of spindle cell phenotype by vascular endothelial cells and NF-kappaB activation plays an essential role in this process.
人类疱疹病毒8型（HHV8），也被称为卡波西肉瘤相关疱疹病毒，与卡波西肉瘤的发生有关，卡波西肉瘤是一种以存在独特的增殖性梭形细胞为特征的疾病。尽管HHV8在体外可诱导血管内皮细胞发生梭形细胞转化，但负责此表型的病毒基因仍有待确定。我们证明，HHV8编码的病毒Fas相关死亡结构域蛋白样白细胞介素-1β转化酶抑制蛋白K13的表达足以在人脐静脉内皮细胞（HUVEC）中诱导梭形细胞表型，这与核因子-κB（NF-κB）途径的激活相关，并且可被该途径的特异性抑制剂Bay-11-7082阻断。K13诱导了几个已知在HHV8转化的血管内皮细胞中上调的基因的表达，如白细胞介素（IL）-6、IL-8、CXC配体3（CXCL3）、孤儿G蛋白偶联受体（RDC1）、环氧化酶-2（COX-2）和双特异性磷酸酶5（DUSP5）。此外，与K13相似，HHV8诱导的HUVEC梭形细胞转化与NF-κB激活相关，并且可被Bay-11-7082阻断。因此，HHV8单个潜伏基因的异位表达足以使血管内皮细胞获得梭形细胞表型，并且NF-κB激活在此过程中起关键作用。
